Immunological insights into COVID-19 in Southern Nigeria.

Introduction: One of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic. Methods: We used spike RBD and N- IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses. Result: Our study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic. Discussion: These findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone.

Clinical characteristics and predictors of human mpox outcome during the 2022 outbreak in Nigeria: a cohort study.

BACKGROUND: Research from sub-Saharan Africa that contributes to our understanding of the 2022 mpox (formerly known as monkeypox) global outbreak is insufficient. Here, we describe the clinical presentation and predictors of severe disease among patients with mpox diagnosed between Feb 1, 2022, and Jan 30, 2023 in Nigeria. METHODS: We did a cohort study among laboratory-confirmed and probable mpox cases seen in 22 mpox-treatment centres and outpatient clinics across Nigeria. All individuals with confirmed and probable mpox were eligible for inclusion. Exclusion criteria were individuals who could not be examined for clinical characterisation and those who had unknown mortality outcomes. Skin lesion swabs or crust samples were collected from each patient for mpox diagnosis by PCR. A structured questionnaire was used to document sociodemographic and clinical data, including HIV status, complications, and treatment outcomes from the time of diagnosis to discharge or death. Severe disease was defined as mpox associated with death or with a life-threatening complication. Two logistic regression models were used to identify clinical characteristics associated with severe disease and potential risk factors for severe disease. The primary outcome was the clinical characteristics of mpox and disease severity. FINDINGS: We enrolled 160 people with mpox from 22 states in Nigeria, including 134 (84%) adults, 114 (71%) males, 46 (29%) females, and 25 (16%) people with HIV. Of the 160 patients, distinct febrile prodrome (n=94, 59%), rash count greater than 250 (90, 56%), concomitant varicella zoster virus infection (n=48, 30%), and hospital admission (n=70, 48%) were observed. Nine (6%) of the 160 patients died, including seven (78%) deaths attributable to sepsis. The clinical features independently associated with severe disease were a rash count greater than 10 000 (adjusted odds ratio 26·1, 95% CI 5·2-135·0, p<0·0001) and confluent or semi-confluent rash (6·7, 95% CI 1·9-23·9). Independent risk factors for severe disease were concomitant varicella zoster virus infection (3·6, 95% CI 1·1-11·5) and advanced HIV disease (35·9, 95% CI 4·1-252·9). INTERPRETATION: During the 2022 global outbreak, mpox in Nigeria was more severe among those with advanced HIV disease and concomitant varicella zoster virus infection. Proactive screening, management of co-infections, the integration and strengthening of mpox and HIV surveillance, and preventive and treatment services should be prioritised in Nigeria and across Africa. FUNDING: None.

The unusual finding of peripheral lymphadenopathy among confirmed Lassa fever patients in Nigeria.

Lassa fever is a viral haemorrhagic fever belonging to the arenaviridae family that is well known to be endemic to West Africa. The clinical presentation of the disease ranges from asymptomatic to fulminant illness. Lymphadenopathy a clinical manifestation of inflammation, infection, or malignancy has not been widely reported in Lassa fever disease. We report two cases of Lassa fever disease presenting with lymphadenopathy.

Enlargement of lymph nodes, is a common symptom of many infections, however it is not commonly mentioned in patients with Lassa fever, a viral hemorrhagic fever that is endemic in West Africa. However, recent research suggests that lymphadenopathy may be underreported in Lassa fever patients. This new finding could have important implications for the diagnosis and treatment of the disease, as well as for our understanding of how it spreads.

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever.

BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.

Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study.

BACKGROUND: Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. METHODS: We did a prospective cohort study (LASCOPE) at the Federal Medical Centre in Owo, Nigeria. All patients admitted with confirmed Lassa fever were invited to participate and asked to give informed consent. Patients of all ages, including newborn infants, were eligible for inclusion, as were pregnant women. All participants received standard supportive care and intravenous ribavirin according to Nigeria Centre for Disease Control guidelines and underwent systematic biological monitoring for 30 days. Patients' characteristics, care received, mortality, and associated factors were recorded using standard WHO forms. We used univariable and multivariable logistic regression models to investigate an association between baseline characteristics and mortality at day 30. FINDINGS: Between April 5, 2018, and March 15, 2020, 534 patients with confirmed Lassa fever were admitted to hospital, of whom 510 (96%) gave consent and were included in the analysis. The cohort included 258 (51%) male patients, 252 (49%) female patients, 426 (84%) adults, and 84 (16%) children (younger than 18 years). The median time between first symptoms and hospital admission was 8 days (IQR 7-13). At baseline, 176 (38%) of 466 patients had a Lassa fever RT-PCR cycle threshold (Ct) lower than 30. From admission to end of follow-up, 120 (25%) of 484 reached a National Early Warning Score (second version; NEWS2) of 7 or higher, 67 (14%) of 495 reached a Kidney Disease-Improving Global Outcome (KDIGO) stage of 2 or higher, and 41 (8%) of 510 underwent dialysis. All patients received ribavirin for a median of 10 days (IQR 9-13). 62 (12%) patients died (57 [13%] adults and five [6%] children). The median time to death was 3 days (1-6). The baseline factors independently associated with mortality were the following: age 45 years or older (adjusted odds ratio 16·30, 95% CI 5·31-50·30), NEWS2 of 7 or higher (4·79, 1·75-13·10), KDIGO grade 2 or higher (7·52, 2·66-21·20), plasma alanine aminotransferase 3 or more times the upper limit of normal (4·96, 1·69-14·60), and Lassa fever RT-PCR Ct value lower than 30 (4·65, 1·50-14·50). INTERPRETATION: Our findings comprehensively document clinical and biological characteristics of patients with Lassa fever and their relationship with mortality, providing prospective estimates that could be useful for designing future therapeutic trials. Such trials comparing new Lassa fever treatments to a standard of care should take no more than 15% as the reference mortality rate and consider adopting a combination of mortality and need for dialysis as the primary endpoint. FUNDING: Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les hépatites virales, French National Research Institute for Sustainable Development.

Lassa fever coinfection with COVID-19 among health care workers: report of two cases

Lassa fever (LF) coinfection with hepatitis B and HIV has been reported among hospitalized patients in Southwest Nigeria and HIV patients coinfected with COVID-19 have been described among hospitalized patients in North Central Nigeria, no study has reported cases of coinfection of Lassa disease and COVID-19 among health care workers (HCWs) worldwide. A case report of two HCWs who were infected with both LF virus and SARS-CoV-2 virus at same time and were successfully managed without any sequelae. Both cases presented with typical signs of LF with COVID-19 suspected, they were promptly diagnosezd with positive outcomes after treatment. While case 1 became negative for LF virus and SARS-CoV-2 after 6 and 30 days, respectively, case 2 became negative for both viruses after 14 and 32 days, respectively. The diagnosis of LF-COVID-19 coinfection in HCWs is a frightening dimension to the health risks faced by HCWs, therefore, HCWs now more than ever before want to know what comes next and how safe is the practice of medicine

Lassa fever coinfection with COVID-19 among health care workers: Report of two cases

Lassa fever (LF) coinfection with hepatitis B and HIV has been reported among hospitalized patients in Southwest Nigeria and HIV patients coinfected with COVID-19 have been described among hospitalized patients in North Central Nigeria, no study has reported cases of coinfection of Lassa disease and COVID-19 among health care workers (HCWs) worldwide. A case report of two HCWs who were infected with both LF virus and SARS-CoV-2 virus at same time and were successfully managed without any sequelae. Both cases presented with typical signs of LF with COVID-19 suspected, they were promptly diagnosed with positive outcomes after treatment. While case 1 became negative for LF virus and SARS-CoV-2 after 6 and 30 days, respectively, case 2 became negative for both viruses after 14 and 32 days, respectively. The diagnosis of LF-COVID-19 coinfection in HCWs is a frightening dimension to the health risks faced by HCWs, therefore, HCWs now more than ever before want to know what comes next and how safe is the practice of medicine.

Association of hypoalbuminemia and reversal of albumin-to-globulin ratio with morbidity outcome among hospitalized Lassa fever infected patients at a dedicated treatment center in Ondo state, south-western Nigeria.

BACKGROUND: As of this present moment, there is paucity of data on report concerning the association between hypoalbuminaemia or reversal of albumin-to-globulin ratio and morbidity outcome in Lassa fever (LF) infection as a crucial determinant prognostic-predictor factor for treatment-survival outcome. AIM: This study was designed to determine the association between hypoalbuminaemia, reversal of albumin-to-globulin ratio and morbidity outcome among confirmed LF infected patients. METHODOLOGY: This was a descriptive retrospective study involving the assessment of records of confirmed LF infected patients that were managed at the center from November 2018 to October 2019. RESULTS: Out of 83 recruited participants with complete records, 66 (79.5%) had hypoalbuminaemia, 74 (89.2%) had reversal of albumin-to-globulin ratio. A higher mean value of total white blood cell (WBC) count was observed among patients with hypoalbuminaemia (p < 0.0001) and reversal of albumin-to-globulin ratio (p < 0.0001) when compared to patients with normal values, respectively. Also, this study showed statistically significant associations between serum albumin level versus total WBC count (p < 0.0001), acute kidney injury (AKI; p = 0.009), bleeding diathesis (p < 0.0001), and occurrence of pregnancy miscarriage (p < 0.0001). CONCLUSION: There is a baseline hypoalbuminaemia and reversal of albumin-to-globulin ratio among confirmed LF infected patients. Based on these findings, the serum level of albumin and albumin-to-globulin ratio at presentation may serve as simple early biomarkers to identify patients at high risk for a complicated clinical course of disease. This study also reveals that those hospitalized LF infected patients with hypoalbuminemia and/or reversal of albumin-to-globulin ratio tend to have leucocytosis and experience prolonged duration of illness.

Prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria.

BACKGROUND: The risk of chronic metformin pharmacotherapy to cause vitamin B12 deficiency and its associated medical complications has been of immense concern among diabetic patients. Some studies have postulated that vitamin B12 deficiency is highly prevalent among chronic metformin-treated adult diabetic patients. AIM: This study aimed to determine the prevalence of vitamin B12 deficiency among metformin-treated and metformin-naïve type 2 diabetes mellitus patients. MATERIALS AND METHODS: This was a case-control, prospective, analytical, observational study of 200 adult participants (100 per group) attending the Endocrinology, Medical Out-patients Clinic of Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria. The participants' serum vitamin B12 levels were determined using an immunoassay technique. Data were presented using tables and charts. Chi-square test was used to compare non-continuous proportional variables. RESULTS: The prevalence of vitamin B12 deficiency was 41% and 20% among metformin-treated and metformin-naïve type 2 diabetes mellitus groups, respectively (p = 0.001). Borderline vitamin B12 status was present among 59% of metformin-treated group and 80% of metformin-naïve group (p = 0.001). Neither metformin-treated nor metformin-naïve groups had normal serum vitamin B12 levels. CONCLUSION: The prevalence of vitamin B12 deficiency was significantly high in diabetics, especially the metformin-treated patients. We advocate for vitamin B12 supplementation among this group of patients in order to prevent the occurrence of vitamin B12 deficiency complications such as macro-ovalocytic anemia, impaired immunity with hypersegmented neutrophils, peripheral neuropathy and subacute degeneration of the spinal cord.